Duodenoesophageal reflux and the development of esophageal adenocarcinoma in rats.

BACKGROUND. The carcinogenic effect of duodenoesophageal reflux, gastroesophageal reflux, and nitrosamines was studied in the rat esophagus. METHODS. Twenty male Sprague-Dawley rats underwent esophagogastroplasty to produce gastroesophageal reflux and 60 underwent duodenoesophageal anastomosis to produce duodenoesophageal reflux. Forty-three animals underwent no operation and acted as controls. Carcinogens known to produce squamous tumors in the rat esophagus (2,6-dimethylnitrosomorpholine [DMNM] or methyl-n-amylnitrosamine [MNAN]) were tested in each group. RESULTS. The rate of squamous carcinoma was 25% for rats with DMNM alone, 30% for rats with MNAN alone, and 20% for rats with induced gastroesophageal reflux plus DMNM. The rate of malignant change rose to 80% in rats with induced duodenoesophageal reflux and DMNM and 67% with duodenoesophageal reflux and MNAN. With duodenoesophageal reflux, 50% of tumors were adenocarcinoma, in contrast to 100% squamous differentiation of tumors in rats given the carcinogens with esophagogastroplasty or no operation. CONCLUSION. The presence of duodenoesophageal reflux increased the frequency and changed the histologic type of esophageal cancer in nitrosamine-treated rats. This indicates that duodenoesophageal reflux plays a role in the development of esophageal adenocarcinoma.     

Reconstitution of (BALB/c x B6)F1 normal mice with stem cells and thymus from nonobese diabetic mice results in autoimmune insulitis of the normal hosts' pancreases.

The NOD mouse develops immune-mediated diabetes mellitus characterized by T cell infiltration and destruction of pancreatic islet tissue. We wished to determine whether one contributing factor was an abnormality of the NOD pancreas that caused it to elicit an attack by NOD T cells. Therefore we constructed mice that had an NOD immune system and a non-NOD host pancreas. We found that these animals with only an NOD immune system developed both insulitis and diabetes in their non-NOD pancreas. We conclude that the NOD pancreas is not unique in its ability to elicit an autoimmune attack from NOD T cells.     

Therapeutic review: antibiotic prophylaxis for bacterial endocarditis

A recent survey of antibiotic prophylaxis found that local practice often differed from that recommended by authoritative bodies such as the British Society for Antimicrobial Chemotherapy (BSAC) and the American Heart Association (AHA). Practitioners found the subject confusing and requested guidance. For these reasons we present current recommendations. Unfortunately all recommendations are based on animal studies and an understanding of the pathogenesis of bacterial endocarditis in humans. There are no controlled trials in humans on which to base guidelines, so rigidity is inappropriate. It is also important to realise that optimal prophylaxis will not eliminate bacterial endocarditis. In developed countries it has been estimated that only 10% of cases of endocarditis are theoretically preventable.     

Fetal pancreas transplantation in miniature swine. IV. Suppression of DTH and MLR responses by treatment with ultraviolet light-irradiated peripheral blood lymphocytes

Irradiation of peripheral blood lymphocytes of miniature swine with ultraviolet light prevented them from initiating proliferative responses in allogeneic mixed lymphocyte reactions and also reduced IL-2 production in these MLRs. When pigs were injected in a series of 4-5 weekly transfusions with UV-irradiated allogeneic PBL differing at the MHC, PBL of recipient pigs progressively responded less strongly to donor PBL in MLRs over the treatment period. These pigs also gave negligible delayed-type hypersensitivity responses to donor PBL at the end of the treatment period. Of the seven UV-irradiated PBL-treated pigs, four produced no antidonor PBL antibody and three produced antibody. Serum from the three antibody-producing pigs also suppressed MLRs of unrelated PBL. By contrast, pigs that received a series of injections of untreated allogeneic PBL gave strong DTH responses to donor PBL and heightened proliferation in MLRs with donor PBL, and all produced antidonor PBL antibody.     

Circadian esophageal motor function in patients with gastroesophageal reflux disease

Effective esophageal peristalsis is a major determinant of esophageal clearance function and may contribute to the development of complications in gastroesophageal reflux disease. Using 24-hour ambulatory esophageal manometry, we compared the circadian esophageal motor activity of normal volunteers to that of patients with increased esophageal exposure to gastric juice and various grades of mucosal injury (no mucosal injury, esophagitis, stricture, or Barrett's esophagus). The prevalence of a mechanically defective lower esophageal sphincter, esophageal acid exposure time, and the frequency of nonperistaltic esophageal contractions during the supine, upright, and meal periods increased with increasing severity of mucosal injury. The median amplitude of esophageal contractions was compromised only in patients with a mechanically defective sphincter. This was particularly so in patients with stricture or Barrett's esophagus and was associated with an increased frequency of ineffective contractions (less than 30 mm Hg). These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be caused by persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. The need for surgical correction of a mechanically defective sphincter before the loss of esophageal body function is implicated.     

Trans-catheter closure of patent ductus arteriosus in childhood--an alternative to surgical ligature]

Transcatheter closure of a persistently patent ductus arteriosus (PDA) was successfully performed in four children using a Rashkind double disk umbrella device. Mean age was 5.1 +/- 1.5 (2.8 to 6.3 years) and weight 18.8 +/- 3.8 kg (14.1 to 22.3 kg). In all children the PDA was the only cardiac lesion and was diagnosed clinically and by means of continuous wave and color-coded doppler echocardiography. After angiographic measurement of PDA size the correlating device was implanted. The ductus was closed immediately in two children, whereas there was a residual angiographic shunt in the others. Echocardiography performed within 24 hours showed a minimal shunt only in one of these cases. The shunt had disappeared at the one month follow up study. We experienced none of the reported possible complications. Transcatheter closure of the PDA after the neonatal period seems to be a safe and effective alternative to surgical ligation as our early experience shows, and should become the procedure of first choice in these patients.